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Paolo Capogrosso, Eugenio Ventimiglia, Marco Moschini, Luca Boeri, Elena Farina, Nadia Finocchio, Giorgio Gandaglia, Nicola Fossati, Alberto Briganti, Franscesco Montorsi, Andrea Salonia
BACKGROUND: Controversial results have shown a significant association with either low or high total testosterone (tT) levels and high risk prostate cancer (PCa). We tested the relationship between circulating tT and grade group 5 (G5) PCa at radical prostatectomy (RP) in patients with preoperative low- to intermediate-risk disease. METHODS: Serum sex hormones were assessed the day before RP in a cohort of 846 patients with low- to intermediate-risk PCa. Patients were segregated using the new 5-tiered Gleason grade groups...
October 24, 2016: Prostate
Abra Jeffers, Vanessa Sochat, Michael W Kattan, Changhong Yu, Erin Melcon, Kosi Yamoah, Timothy R Rebbeck, Alice S Whittemore
BACKGROUND: Prostate cancer prognosis is variable, and management decisions involve balancing patients' risks of recurrence and recurrence-free death. Moreover, the roles of body mass index (BMI) and race in risk of recurrence are controversial [1,2]. To address these issues, we developed and cross-validated RAPS (Risks After Prostate Surgery), a personal prediction model for biochemical recurrence (BCR) within 10 years of radical prostatectomy (RP) that includes BMI and race as possible predictors, and recurrence-free death as a competing risk...
October 24, 2016: Prostate
Takashi Dejima, Kenjiro Imada, Ario Takeuchi, Masaki Shiota, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Ladan Fazli, Seiji Naito, Martin E Gleave, Christopher J Ong
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy...
October 24, 2016: Prostate
Milan S Geybels, Karen D McCloskey, Ian G Mills, Janet L Stanford
BACKGROUND: Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. METHODS: Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005)...
October 18, 2016: Prostate
Paolo Dell'Oglio, Robert Jeffrey Karnes, Giorgio Gandaglia, Nicola Fossati, Armando Stabile, Marco Moschini, Vito Cucchiara, Emanuele Zaffuto, Pierre I Karakiewicz, Nazareno Suardi, Francesco Montorsi, Alberto Briganti
BACKGROUND: A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five-tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR). METHODS: Between 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers...
October 18, 2016: Prostate
Damien A Leach, Andrew P Trotta, Eleanor F Need, Gail P Risbridger, Renea A Taylor, Grant Buchanan
BACKGROUND: Improving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer-specific survival, and that stromal AR reduces metastasis...
October 8, 2016: Prostate
Junnan Liu, Maolin Xiao, Jianjun Li, Delin Wang, Yunfeng He, Jiang He, Fei Gao, Li Mai, Ying Li, Yong Liang, Yuejiang Liu, Xiaoni Zhong
BACKGROUND: Currently, the role of UPR signaling in prostate cancer (PCa) is unclear. To evaluate the relationship between UPR signaling pathway and the prognosis of PCa, we explored the expression of IRE1, PERK, and ATF6 in tissues. METHODS: A total of 160 PCa and 30 benign prostate hyperplasia (BPH) tissues were collected. The expression of UPR signaling factors was assessed by immunohistochemistry. The staining characteristics were identified and evaluated for associations with clinicopathologic parameters, PSA recurrence survival, and prostate cancer-specific morality...
October 8, 2016: Prostate
Adam T Szafran, Cliff Stephan, Michael Bolt, Maureen G Mancini, Marco Marcelli, Michael A Mancini
BACKGROUND: AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood...
October 4, 2016: Prostate
Katie M Di Sebastiano, Jehonathan H Pinthus, Wilhelmina C M Duivenvoorden, Laurel Patterson, Joel A Dubin, Marina Mourtzakis
BACKGROUND: Prostate cancer development is associated with numerous lifestyle factors (i.e., physical activity, nutrition intake) and metabolic perturbations. These factors have been studied independently; here, we used an integrative approach to characterize these lifestyle and metabolic parameters in men undergoing diagnostic prostate biopsies. METHODS: We prospectively evaluated 51 consecutive men for body composition, metabolic factors including glucose- and lipid-related measures, as well as lifestyle factors prior to prostate biopsy...
October 4, 2016: Prostate
Maria L Breser, Ruben D Motrich, Leonardo R Sanchez, Virginia E Rivero
BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant...
October 4, 2016: Prostate
Azza Shoaibi, Gowtham A Rao, Bo Cai, John Rawl, Kathlyn Sue Haddock, James R Hébert
PURPOSE: To investigate if a prostate specific antigen (PSA)-derived growth curve can predict the occurrence of high-risk prostate cancer (PrCA). METHODS: Data from 38,340 men randomized to the PrCA screening arm in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) were used to develop a PSA growth curve model to estimate PSA rate of change. The model was then used to predict high-risk PrCA in clinical data available from 680,390 veterans seeking routine care...
October 4, 2016: Prostate
Kenjiro Imada, Masaki Shiota, Kentaro Kuroiwa, Masaaki Sugimoto, Tatsuro Abe, Kenichi Kohashi, Akira Yokomizo, Masatoshi Eto, Seiji Naito, Yoshinao Oda
BACKGROUND: FOXO3a is a member of the forkhead O transcription factors. FOXO3a induces the factors that contribute to cell cycle arrest and is considered a tumor suppressor in several malignant tumors. Y-box binding protein-1 (YB-1) is a multifunctional protein whose high expression is correlated with poor prognoses in various malignant tumors. In the current study, we investigated the relationship between FOXO3a and YB-1 to validate their functional roles in prostate cancer. METHODS: Western blotting and cytotoxicity assays were conducted in prostate cancer cells, LNCaP, and 22Rv1 cells...
October 4, 2016: Prostate
Hideo Otsuki, Toru Kimura, Takashi Yamaga, Takeo Kosaka, Jun-Ichi Suehiro, Hiroyuki Sakurai
BACKGROUND: Leucine stimulates cancer cell proliferation through the mTOR pathway, therefore, inhibiting leucine transporters may be a novel therapeutic target for cancer. L-type amino acid transporter (LAT) 1, a Na(+) -independent amino acid transporter, is highly expressed in many tumor cells. However, leucine transporter(s) in different stages of prostate cancer, particularly in the stages of castration resistance with androgen receptor (AR) expression, is unclear. METHODS: LNCaP and DU145 and PC-3 cell lines were used as a model of androgen dependent, and metastatic prostate cancer...
October 3, 2016: Prostate
Vincenzo N Talesa, Ivana Ferri, Guido Bellezza, Harold D Love, Angelo Sidoni, Cinzia Antognelli
BACKGROUND: Glyoxalase 2 (Glo2), together with glyoxalase 1 (Glo1), forms the main scavenging system of methylglyoxal, a potent pro-apoptotic agent mainly generated by glycolysis. An increased rate of glycolysis is a well known signature of cancer cells. As a survival strategy, Glo1 is overexpressed in many human malignant cells, including prostate cancer (PCa), where it plays a crucial role in progression. No information is available on the role of Glo2 in the same ambit. PCa is the most common malignancy affecting men in the western world...
October 3, 2016: Prostate
Yasuhito Funahashi, Tsuyoshi Majima, Yoshihisa Matsukawa, Tokunori Yamamoto, Masaki Yoshida, Momokazu Gotoh
BACKGROUND: We examined whether urine reflux into the prostate can induce prostatic inflammation in a rat and evaluated the effect of α1-adrenoreceptor antagonist. METHODS: Experiment 1: Male Sprague-Dawley rats were injected with 500 µl of Evans Blue through the urethral orifice. Intravesical pressure was measured, and the prostate was excised to evaluate urine reflux. Experiment 2: Rats were injected with 500 µl urine or saline (control) from the urethral orifice...
September 29, 2016: Prostate
Zachary S Zumsteg, Zinan Chen, Lauren E Howard, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Daniel E Spratt, Howard M Sandler, Stephen J Freedland
BACKGROUND: To validate and further improve the stratification of intermediate risk prostate cancer into favorable and unfavorable subgroups for patients undergoing radical prostatectomy. MATERIALS AND METHODS: The SEARCH database was queried for IR patients undergoing radical prostatectomy without adjuvant radiotherapy. UIR disease was defined any patient with at least one unfavorable risk factor (URF), including primary Gleason pattern 4, 50% of more biopsy cores containing cancer, or multiple National Comprehensive Cancer Network IR factors...
September 29, 2016: Prostate
Sami-Ramzi Leyh-Bannurah, Stéphanie Gazdovich, Lars Budäus, Emanuele Zaffuto, Paolo Dell'Oglio, Alberto Briganti, Firas Abdollah, Francesco Montorsi, Jonas Schiffmann, Mani Menon, Shahrokh F Shariat, Margit Fisch, Felix Chun, Markus Graefen, Pierre I Karakiewicz
OBJECTIVE: To externally validate the updated 2012 Partin Tables in contemporary North American patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) at community institutions. MATERIALS AND METHODS: We examined records of 25,254 patients treated with RP and pelvic lymph node dissection (PLND) between 2010 and 2013, within the surveillance, epidemiology, and end results database. The ROC derived AUC assessed discriminant properties of the updated 2012 Partin Tables of organ confined disease (OC), extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI)...
September 29, 2016: Prostate
Andrea K Miyahira, Sameek Roychowdhury, Sangeeta Goswami, Joseph E Ippolito, Saul J Priceman, Colin C Pritchard, Karen S Sfanos, Sumit K Subudhi, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. METHODS: For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer...
September 28, 2016: Prostate
Cachétne S X Barrett, Ana C Millena, Shafiq A Khan
BACKGROUND: Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival...
September 7, 2016: Prostate
Wahyu Wulaningsih, Yuliana Astuti, Tetsuya Matsuguchi, Putri Anggrandariyanny, Johnathan Watkins
BACKGROUND: We investigated the association of prostate-specific antigen (PSA) with leukocyte telomere length, which may be altered in preclinical prostate malignancies. METHODS: This study was based on the 2001-2002 U.S. National Health and Nutrition Examination Survey (NHANES). A subsample of 1,127 men aged 40-85 years without prior history of prostate cancer who provided informed consent and blood samples were selected. Leukocyte telomere length (LTL) relative to standard DNA reference (T/S ratio) was quantified by polymerase chain reaction (PCR)...
August 27, 2016: Prostate
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